The Radiation Oncology and Surgery Branches of the National Cancer Institute have been involved in prospective randomized trials evaluating the potential role of intraoperative radiotherapy in three major disease sites including resectable carcinomas of the pancreas, resectable carcinomas of the stomach and resectable retroperitoneal sarcomas. We have also been involved in a single arm pilot trial involved in dose escalation of intraoperative therapy in selected patients whose locally advanced tumor are felt unlikely to be cured by standard therapy and at least there is a theoretical advantage for the use of intraoperative radiation therapy. Finally, as of September, 1983, we are involved in a randomized prospective trial evaluating a combination of intraoperative radiation and external beam radiation compared to conventional external beam radiation alone in patients with unresectable pancreatic carcinomas. To date, 80 patients have been treated with experimental intraoperative radiation therapy on these various protocols and there are an additional 45 other patients being followed as control patients on the various randomized prospective trials. We have clearly demonstrated that it is technically possible to combine intraoperative radiation therapy with a radical surgical procedure and that the acute morbidity from the combination is quite acceptable. To date, there does not appear to be any significant difference in the randomized prospective trials with respect to a local control, disease free survival, and overall survival. Obviously, these trials are ongoing and require more patients and further follow-up. Patients also need to be followed for any potential late effects of intraoperative radiation therapy.